PROJECT SUMMARY Fibrosis-related late effects of head and neck cancer (HNC) cause crippling loss of swallowing function (dysphagia). Among HNC survivors with late radiation-associated dysphagia (late-RAD), our prior published work finds significant functional loss over time despite standard therapies. New therapy strategies are badly needed. Recent pilot data from our group suggest promise of adjunctive manual therapy (MT) in HNC survivors with fibrosis-related late effects. In 15 patients, we observed significant gains in cervical range of motion, improving on average 11-degrees after a single session of MT (p<0.001), and survivors offered remarkable qualitative reports of functional gains when MT was applied in the clinic. Yet, to date, no peer review published work has examined the therapeutic potential of MT for late fibrosis-related swallowing dysfunction. As such, there is no algorithm for use of this promising therapy. Prospective, systematic efforts are desperately needed to understand functional translation, dose, and durability of adjunctive MT as it relates to swallowing rehabilitation in this profoundly challenging clinical population. The proposed pilot project (the ManTLE trial: Manual Therapy for Late Effect Dysphagia) is aimed at investigating manual therapy as it relates to fibrosis-related late dysphagia. We propose a 12-week, single-arm pilot clinical trial in 24 HNC survivors with late dysphagia. Coupling advanced imaging with multimodal clinician and patient-reported assessments, we expect to understand the functional translation of manual therapy to swallowing in HNC survivors suffering late effects of therapy. The specific aims of this application include: 1) examine dose-response and durability of MT for cervical extension in HNC survivors with fibrosis-related late effects, and 2) examine functional translation of MT to swallowing in HNC survivors with fibrosis-related late effects. Our central hypothesis is that normalized cervical extension after MT is associated with improved swallowing function in HNC survivors with fibrosis-related late-RAD. These pilot data are essential to determine the rationale and feasibility of larger hypothesis-driven therapeutic trials ultimately aiming to improve swallowing function, health, and quality of life (QOL) in HNC survivorship. This is an unprecedented time in HNC survivorship, wherein epidemiologic shifts in recent decades have led to rapidly growing numbers of survivors who suffer with fibrosis-related late effects. With grim results of current therapies, novel strategies are critical to improve QOL and health in survivors.